The Virology Program Project continues its focus on the identification of interactions between viral and cellular proteins in herpesvirus infection and the effects of viral infection on cellular growth control. The program project includes basic studies of protein/DNA interactions on origins of replication, viral regulation of expression, viral effects on cell function, and the effects of tumor suppressor loss on viral tumorigenesis. Dr. Jack Griffith will continue his studies of herpes simplex virus (HSV) replication proteins, characterizing the replication complex on ori-S and the role of recombination proteins in initiation of replication. Dr. Shannon Kenney will pursue her studies of the Epstein Barr virus (EBV) ori-lyt and the role of BMRF1, the EBV polymerase processivity factor, and the Z and R transactivators and their effects on ori-lyt methylation and cellular repair mechanism. Dr. Joseph Pagano will continue his studies of Type III latency. He will analyze cell cycle effects and the role of the beta-catenin/TCF pathway in regulation of Type III latency. Dr. Eng Shang Huang has shown that HCMV gB binds to and activates the epidermal growth factor receptor. During this funding period, he will further characterize this interaction and, identify the domains of gB and EGFR that interact and develop a bacmid system to produce gB mutants in the context of the virus. Dr. Nancy Raab-Traub, Principal Investigator, will continue her studies of LMP1-induced transformation in transgenic mice and in rodent fibroblasts. She will further characterize the synergistic effects of loss of p16Ink4/p19ARF and LMP1 expression on lymphomagenesis and analyze transgenic mice that express both LMP1 and LMP2 in lymphocytes and epithelial cells. Overall, the Program Project will-continue to dissect the viral/cellular molecular interactions that occur during viral infection and determine how specific molecular events contribute to herpesvirus pathogenesis.